The overall objective of this protocol is to determine the toxicity and MTD of the combination of docetaxel (Taxotere) and G3139, an antisense therapeutic compound directed against Bcl-2. Patients with metastatic breast cancer or other malignancies will be treated with G3139, given as a continuous IV infusion over 21 days, and weekly docetaxel at 35mg/m2. G3139 will be dose escalated between cohorts of 3 patients, until DLT is observed. A total of 6 patients will be treated at the MTD (the dose at which <2 of 6 patients experience DLT). The dose level immediately below MTD (MTD-1) will be selected for future phase II study. Previous studies suggest that G3139 is well tolerated in humans, induces high rates of apoptosis in Bcl-2-expressing tumors, induces clinical responses in chemotherapy-refractory NHL, and may vary resistance to chemotherapeutic agents that function through apoptotic mechanisms. Therefore, the proposed phase I-Iia trial combining docetaxel (Taxotere) and G3139 in a phase I trial to determine whether these agents can be safely co-administered, and whether this combination results in clinical responses in patients with disease that is refractory or resistant to prior taxane therapy. Expression of the BCL-2 protein confers resistance to various apoptotic triggers, including microtubule disturbance. G3139 (Genta, Inc.) is a phosphorothioate oligonucleotide targeting the bcl-2 mRNA and has been shown to downregulate the BCL-2 protein in vivo. In human breast cancer xenograft models, cotreatment of G3139 with sub-therapeutic dose of docetaxel dramatically enhanced the antitumor effect, leading to complete and durable tumor regression. The current Phase I study seeks to determine the maximum tolerated dose (MTD) and pharmacokinetics of the combined therapy of G3139 and docetaxel in patients with advanced solid tumors. In a 28-day cycle, G3139 is administered as 21-day continuous infusion in addition to weekly docetaxel (35 mg/m2) on day 8, 15 and 22. Eight evaluable patients have received 0.4-4 cycles, with G3139 at escalating doses of 1, 2 and 3 mg/kg/d. All patients had documented BCL-2 expression in the tumors; histologies included breast (5), head and neck (1), non-small cell lung (1) and small cell carcinoma (1). Grade 3 thrombocytopenia was observed in 1 patient (3 mg/kg/d) with small cell carcinoma and history of pelvic radiation who was found to have myelophthisis with extensive tumor infiltration. Transient grade 3 thrombocytopenia was also seen in 1 patient during intra-patient dose escalation. Other side effects included: Grade 1-2 fatigue, Grade 1 mucositis, Grade 2 neutropenia (1 patient) and Grade 1 transaminitis (1 patient). Serial analysis of the peripheral blood lymphocyte demonstrated BCL-2 downregulation at G3139 doses of & 2 mg/kg/d. At dose level of 3 mg/kg/d (plasma level > 1.5 &g/ml), maximum BCL-2 reduction could be seen by D3 of the G3139 infusion. Tumor response was observed in 2 patients with breast cancer. We conclude that G3139 and weekly docetaxel at the doses tested is a tolerable combination, and that modulation of BCL-2 could be achieved as seen in PBL. MTD has not been reached and patient accrual continues. These initial data support further development of G3139 in combination with docetaxel, especially for patients with tumors where taxanes has known activity and BCL-2 is upregulated.